DESCRIPTION: This epidemiologic study will evaluate the potential endocrine and reproductive ramifications in human males of exposures to environmental concentrations of perfluourinated chemicals, including perfluourooctylsulfonate (PFOS) and perfluoroocatanoate (PFOA). Products containing these chemicals were recently withdrawn from the market by a major manufacturer amid concerns of persistence, toxicity, and widespread population exposures to these chemicals. The proposed study will focus on the semen quality and endocrine status of a potentially susceptible subpopulation, i.e., men of couples who present at a fertility clinic. It will use a case-control design in that the study population will include a high prevalence of men experiencing reproductive problems ("cases") as well as men with a normal fertility status ("controls"). By using a case-control design (the approach of choice for investigating rare outcomes), the study will be able to efficiently detect any important exposure-related reproductive problems. If exposure levels are associated with male reproductive problems, the study participants are expected to represent a range of exposure to PFOA and PFOS, which will be measured in samples of blood and semen; concentrations in these biological media will reflect the multi-route exposures to these chemicals experienced by virtually all people in our society. Semen quality will be assessed using both routine measures and a test designed to more accurately and reproducibly assess normal, motile, and fertile sperm. Measurements of Follicle Stimulating Hormone, Luteinizing Hormone, Prolactin, Estradiol and free and total Testosterone will reflect the hormonal status of the males and will provide evidence of perturbed endocrine function. If the exposure effect is limited to a sensitive subset of the general population, our study is more likely to detect an association compared to studies that sample on PFOA/PFOS exposure status in an occupational setting.